rs1640945597

Variant names:

• chr1-1293676-C-A
• rs1640945597
• NM_030649.3:c.2393G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-1293676-C-A
• chr1-1293676-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030649.3(ACAP3):​c.2393G>T​(p.Arg798Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000687 in 145,654 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACAP3 NM_030649.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36
• Publications: 0 publications found

Genes affected

ACAP3 (HGNC:16754): (ArfGAP with coiled-coil, ankyrin repeat and PH domains 3) Predicted to enable GTPase activator activity and metal ion binding activity. Predicted to be involved in regulation of catalytic activity. Predicted to act upstream of or within neuron migration and regulation of neuron projection development. Predicted to be located in growth cone. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030649.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAP3	NM_030649.3	MANE Select	c.2393G>T	p.Arg798Leu	missense	Exon 24 of 24	NP_085152.2	Q96P50-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAP3	ENST00000354700.10	TSL:1 MANE Select	c.2393G>T	p.Arg798Leu	missense	Exon 24 of 24	ENSP00000346733.5	Q96P50-3
	ACAP3	ENST00000353662.4	TSL:1	c.2168G>T	p.Arg723Leu	missense	Exon 21 of 21	ENSP00000321139.4	Q96P50-1
	ACAP3	ENST00000467278.5	TSL:1	n.1919G>T		non_coding_transcript_exon	Exon 14 of 14

Frequencies

GnomAD3 genomes AF: 0.00000687 AC: 1 AN: 145654 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000680

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1307944 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 645184

African (AFR) AF: 0.00 AC: 0 AN: 25354

American (AMR) AF: 0.00 AC: 0 AN: 22602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21716

East Asian (EAS) AF: 0.00 AC: 0 AN: 29644

South Asian (SAS) AF: 0.00 AC: 0 AN: 72092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5140

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1045342

Other (OTH) AF: 0.00 AC: 0 AN: 53872

GnomAD4 genome AF: 0.00000687 AC: 1 AN: 145654 Hom.: 0 Cov.: 33 AF XY: 0.0000141 AC XY: 1 AN XY: 71036

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 39436

American (AMR) AF: 0.0000680 AC: 1 AN: 14714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3408

East Asian (EAS) AF: 0.00 AC: 0 AN: 4976

South Asian (SAS) AF: 0.00 AC: 0 AN: 4690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65346

Other (OTH) AF: 0.00 AC: 0 AN: 2004

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		4.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.20
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.68	P
Vest4		0.36
MutPred		0.44		Loss of disorder (P = 0.0753)
MVP		0.58
MPC		0.82
ClinPred		0.99	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.52
gMVP		0.84
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1640945597; hg19: chr1-1229056;